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Role of PI3K/AKT/mTOR Pathway Associated Oxidative Stress and Cardiac Dysfunction in Takotsubo Syndrome

[ Vol. 17 , Issue. 1 ]

Author(s):

Shan Mao, Xianghong Luo, Yu Li, Chaorong He, Fuhua Huang and Cunhua Su*   Pages 35 - 43 ( 9 )

Abstract:


Introduction: Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, but the accurate cause of this syndrome is still unknown.

Methods: β-adrenergic agonist isoproterenol (ISO) is used to establish the TTS rats model. TTS rats were treated with or without LY294002 or Rapamycin. The rat cardiomyoblast cell line H9C2 was subjected to infect with constitutively active Akt (myr-Akt) or dominant-negative mutant Akt (dn-Akt) and then, treated with ISO. Cell apoptosis was assessed using the Bax/ Bcl-2 ratio. In addition, reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE). Mitochondrial superoxide generation and membrane potential were assayed by MitoSOX and JC-1 fluorescence intensity.

Results: ISO might induce the erratic acute cardiac dysfunction and overexpression of PI3K/AKT/mTOR. Moreover, it also increased the oxidative stress and apoptosis in TTS rats. The Akt inhibitor significantly reversed the cardiac injury effect, which triggered by ISO treatment. In H9C2 cells, the inhibition of Akt provides a protective role against ISO-induced injury by reducing oxidative stress, apoptosis and mitochondrial dysfunction.

Conclusion: This study provided new insight into the protective effects of myocardial dysfunction in TTS rats via chronic inhibition of the PI3K/AKT/mTOR expression, which could reduce mitochondrial ROS and oxidative stress-induced apoptosis. PI3K/AKT/mTOR inhibitor could be a therapeutic target to treat cardiovascular dysfunction induced by stress cardiomyopathy.

Keywords:

Takotsubo syndrome, PI3K/AKT/mTOR signaling pathway, ROS, mitochondrial dysfunction, stress, adrenoceptor.

Affiliation:

Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Hubei, 442000, Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Hubei, 442000, Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Hubei, 442000, Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Hubei, 442000, Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, JiangSu, 210006, Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, JiangSu, 210006



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